Prorenin/renin receptor, signals, and therapeutic efficacy of receptor blocker in end-organ damage.
Discovery of prorenin/renin, or (pro)renin, receptor uncovered a novel function of (pro)renin as receptor ligand in addition to enzyme and its precursor; the same receptor was shown to promote reversible activation of prorenin and enhance the enzyme activity of mature renin. Stimulating the receptor activates mitogen-activated protein kinase and hypertrophic, hyperplastic, profibrotic, and cyclooxygenase-2-activating signals. These receptor signals were transmitted independently of angiotensin (Ang) II receptor. A specific blocker of the receptor was discovered-a peptide segment in prorenin that binds to the receptor and blocks ligand binding. Its infusion in animal models of hypertension and diabetes not only prevented nephropathy and cardiac hypertrophy, but also caused regression of nephropathy, whereas Ang II receptor gene deletion and angiotensin-converting enzyme inhibition merely delayed the onset or ameliorated pathologic phenotypes. These results suggest that (pro)renin receptor is responsible for end-organ damage.
Inagami
Tadashi
T
Department of Biochemistry, Vanderbilt University School of Medicine, 663 LH, 23rd Avenue South at Pierce, Nashville, TN 37232, USA. tadashi.inagami@vanderbilt.edu
Ichihara
Atsuhiro
A
D000959:Antihypertensive Agents / Q000627:therapeutic use; D048909:Diabetes Complications; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D012083:Renin / Q000502:physiology*; D012307:Risk Factors; D015398:Signal Transduction; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D000093342:Prorenin Receptor
C458319:ATP6AP2 protein, human; D000959:Antihypertensive Agents; D011956:Receptors, Cell Surface; D012083:Renin; D025262:Vacuolar Proton-Translocating ATPases; D000093342:Prorenin Receptor